During the past year, the VRC's Vector Core created and tested new vaccine vectors expressing different HIV protein, including novel forms of envelope proteins. In addition,different methods and routes of administration as well as prime/boost combinations were tested to further optimize HIV vaccine strategies. New human and nonhuman seroptypes of adenoviral,LCMV and BCG vectors were tested, as well as administration via different routes of delivery. Several candidate vaccines elicited promising immunogenicity data in preliminary studies and are being tested further. Antibodies that inhibit or prevent infection were developed,and initial testing performed. Specific accomplishments include: Continued assessment of recombinant lymphocytic choriomeningitis virus (rLCMV)as a vaccine to prevent HIV infections. Different prime boost vectors encoding HIV-1 Env including DNA, non human primate adenoviruses and alternative serotype rAd for priming followed by boosting with a replication-defective vectors were compared. T cell immunogenicity was assessed by intracellular cytokine staining or by analyzing tetramer positive cells. Studies to optimize the CD4-binding site (CD4bs) as a basis for vaccine development were conducted. The HIV Outer domain (OD) of gp120 envelope is a minimal unit containing the CD4bs which is targeted by broadly neutralizing antibodies, VRC01 and b12, therefore thought to be an attractive immunogen to induce such antibodies. During the past year studies continued to engineer the OD to optimize its use as an immunogen. In addition, a panel of resurfaced core (RSC3)-based glycan molecules and ferritin nanoparticles experssing HIV envelope were designed to induce CD4bs antibodies, identified by newly developed assays based on the resurfaced stabilized gp120 core with antigenic specificity for the initial site of CD4 attachment of gp120. Vectors expressing recently identified VRC01 and other HIV neutralizing antibodies were also developed and analyzed and are being optimized for further testing of their ability to protect against HIV and to induce similar neutralizing antibodies in vivo when used as a vaccine.